Although mAbs present a different set of challenges from other product classes, and the pre-clinical safety evaluation may need to be more extensive than for other medicinal products to overcome the limited predictive value of conventional pre-clinical test systems, the level of risk associated with first administration to human subjects can be effectively mitigated.This article seeks to provide a systematic approach to identifying and addressing the pertinent risks relative to the characteristics of the particular mAb product before the first administration to human subjects.